The broad objectives of the proposed research are to develop and apply methods for the determination of the molecular structure of peptides and proteins in solution. The ultimate aims of this work include the understanding of (a) certain protein structure: function relationships, (b) some of the mechanisms of cation transport through membranes, and (c) the nature and spatial relationships of certain membrane proteins. A major effort will be directed toward the determination of cyclic peptide conformations in lipid bilayers, both in the presence and absence of metal ions. Another part of the effort will be directed towards understanding proteolytic enzyme: substrate and inhibitor interactions at a molecular level. To obtain both of these objectives, use will be made of proton, 13C, and, particularly, 19F nuclear magnetic resonance spectroscopy as well as circular dichroism. The third major, and new, approach proposed is the development of fluorescent photoaffinity labels. Through the use of specific labels for certain membrane-bound enzymes, we will be able to obtain information about the nature of their active sites and, hopefully, obtain information about certain spatial relationships.